The long-term goal of the research proposed is to elucidate the manner in which anesthesia alters metabolism, circulation, and respiration and therefore occasions special considerations prior to and during clinical applications. More specifically, we propose to determine the individual organ contributions to the whole body change in O2 uptake during anesthesia with two new agents, isoflurane and enflurane, and the mechanism involved, as we have previously accomplished for halothane. We propose to extend our studies of the role of anesthetic agents in modifying the response to the stress of hemorrhagic hypotension, the contribution of the sympathoadrenal system to this response, and the therapeutic implications of our findings. We propose to determine the effects of isoflurane and enflurane on cerebral metabolism and circulation and to examine the relative merits of induced hypotension occasioned by either trimetaphan, halothane, or nitroprusside. The relative roles of "red" and "white" muscle in stress responses during anesthesia will be examined as will the effect of various anesthetics on the metabolic response of skeletal muscle to succinylcholine. A major effort will be made to determine the dimensions of the metabolic and circulatory responses of hyperthermic stress-susceptible swine, the target organ, the mechanism involved, the spectrum of anesthetics and drugs capable of inducing the response, and the most effective therapeutics. BIBLIOGRAPHIC REFERENCES: Gronert, G.A., Theye, R.A.: Porcine malignant hyperthermia: metabolic and hemodynamic changes. Anesthesiology. 44: 36-43 (Jan.) 1976. Gronert, G.A., Milde, J.H., Theye, R.A.: Porcine malignant hyperthermia induced by halothane and succinylcholine: failure of treatment with procaine or procainamide. Anesthesiology. 44:124-132 (Feb.) 1976.